Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice.

Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. Abstract Text:

Wei Wang,Einath Zolty,Sandor Falk,Sandra Summer,Robert Stearman,Mark Geraci,Robert Schrier,

Sepsis-related acute kidney injury (AKI) is the leading cause of AKI in intensive care units. Endotoxin is a primary initiator of inflammatory and hemodynamic consequences of sepsis and is associated with experimental AKI. The present study was undertaken to further examine the role of the endothelium, specifically prostacyclin (PGI(2)), in the pathogenesis of endotoxemia-related AKI. A low dose of endotoxin (LPS, 1 mg/kg) in wild-type (WT) mice was associated with stable glomerular filtration rate (GFR) (164.0 +/- 16.7 vs. 173.3 +/- 6.7 microl/min, P = not significant) as urinary excretion of 6-keto-PGF(1alpha), the major metabolite of PGI(2), increased. When cyclooxygenase inhibition with indomethacin abolished this rise in 6-keto-PGF(1alpha), the same low dose of LPS significantly decreased GFR (110.7 +/- 12.1 vs. 173.3 +/- 6.7 microl/min, P < 0.05). The same dose of indomethacin did not alter GFR in WT mice. To further study the role of PGI(2) in endotoxemia, renal-specific PGI synthase (PGIs) transgenic (Tg) mice were developed that had increased PGIs expression only in the kidney and increased urinary 6-keto-PGF(1alpha). These Tg mice, however, demonstrated endotoxemia-related AKI with low-dose LPS (1 mg/kg) (GFR: 12.6 +/- 3.9 vs. 196.5 +/- 21.0 microl/min P < 0.01), which did not alter GFR in WT mice (164.0 +/- 16.7 vs. 173.3 +/- 6.7 microl/min, P = not significant). An elevation in renal cAMP, however, suggested an activation of the PGI(2)-cAMP-renin system in these Tg mice. Moreover, angiotensin-converting enzyme inhibition afforded protection against endotoxin-related AKI in these Tg mice. Thus endothelial PGIs-mediated PGI(2), as previously shown with endothelial nitric oxide synthase-mediated nitric oxide, contributes to renal protection against endotoxemia-related AKI. This effect may be overridden by excessive activation of the renin-angiotensin system in renal-specific PGIs Tg mice.

Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. Publishing Authors By Initials

W Wang,E Zolty,S Falk,S Summer,R Stearman,M Geraci,R Schrier,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of physiology. Renal physiology

VOLUME: 293

Page Numbers: F1131-6

Journal Abbreviation: Am. J. Physiol. Renal Physiol.

ISSN: 0363-6127

DAY: 25

MONTH: 07

YEAR: 2007

Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100901990

Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice.

AFFILIATION: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA. robert.schrier@uchsc.edu).

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Am J Physiol Renal Physiol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice Related Publications

• Analysis of N-ras mutations in human cutaneous melanoma: tumor heterogeneity detected by polymerase chain reaction/single-stranded conformation polymorphism analysis.
• Aquaporin-related disorders of water homeostasis.
• Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome.
• Calcium channel blockers: protective effects in ischemic acute renal failure.
• Decreased effective blood volume in edematous disorders: what does this mean?
• Developments in the management of autosomal dominant polycystic kidney disease.
• Efficient Synthetic Access to a New Family of Highly Potent Bryostatin Analogues via a Prins-Driven Macrocyclization Strategy.
• Endotoxemia-related acute kidney injury in transgenic mice with endothelial overexpression of GTP cyclohydrolase-1.
• Further in vivo evidence for antagonist-to-antidiuretic action of arginine vasopressin.
• Hyperosmolality in vivo upregulates aquaporin 2 water channel and Na-K-2Cl co-transporter in Brattleboro rats.
• Induced alterations in calcium uptake rate in normoxic rate proximal tubules.
• Molecular mechanisms of antidiuretic effect of oxytocin.
• Molecular mechanisms of clinical concentrating and diluting disorders.
• Nepafenac-associated corneal melt.
• Nitric oxide synthase inhibition and acute renal ischemia: effect on systemic hemodynamics and mortality.
• Polyuria of thyrotoxicosis: downregulation of aquaporin water channels and increased solute excretion.
• Potential pharmacological interventions in polycystic kidney disease.
• Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice.
• Relationship between urinary albumin excretion and left ventricular mass with mortality in patients with type 2 diabetes.
• Role of AQP1 in endotoxemia-induced acute kidney injury.
• Sarcoidosis of the nervous system.
• The role of calcium in the pathogenesis of acute renal failure.
• The role of the calcium-dependent enzymes nitric oxide synthase and calpain in hypoxia-induced proximal tubule injury.
• The sea within us: disorders of body water homeostasis.
• Therapy of acute myelocytic leukemia. Daunomycin contrasted with a combination of cytosine arabinoside and 6-thioguanine.
• Tribromethanol (Avertin).
• Variation in age at ESRD in autosomal dominant polycystic kidney disease.
• Vascular effects of arginine vasopressin, angiotensin II, and norepinephrine in adrenal insufficiency.
• Vascular effects of arginine-vasopressin, angiotensin and noradrenaline in adrenal insufficiency.
• Vasopressin and aquaporin 2 in clinical disorders of water homeostasis.